The infectious disease from Vibrio vulnificus or its abbreviation “V. vulnificus” has a relatively short history, but clinical cases have been reported continuously worldwide and this disease is one of the newly obserbed diseases. Although the absolute number of clinical cases of this disease is less than that of cholera or salmonella food poisoning, it raises a significant social problem due to its high mortality rate and tragic clinical manifestations.
V. vulnificus was first reported in 1976 by Hollis et al. of CDC (Centers for Disease Control in USA) after they studied bacteriological properties of halophilic, pathogenic Vibrio that was isolated from human for 11 years, and named lactose-fermenting Vibrio or Lac(+) due to its feature of lactose fermenting. In 1979, Blake el al. of CDC classified 39 patients reported in CDC to primary septicemia and wound infection groups according to clinical manifestations analyzed by epidemiology (Blake, P. A., Merson M. H., Weaver, R. E., Hollis, D. G., Heublin, P. C., N. EngL J. Med 300:1-6, 1979). In the same year, Farmer named it Vibrio vulnificus (vulnus=wound, ficus=forming) as a new species. (Farmer, J. J. III, Lancet 2 :903, 1979).
Infections from pathogenic bacteria and viruses are progressed mostly through the mucosal route via aspiration, oral intake and sexual transmission etc. In adult, the surface area of respiratory, digestive, and genitourinary systems that covered by a mucosal surface is approximately 400 m2. The primary defense system against normal flora and invasion of viruses and bacteria originated from the external environment relates mainly to the mucosal immune response. The mucosal immunity involved mainly in the mucosal surface has not yet been studied in depth in comparison to the systemic immunity, but there is no doubt about its importance. Recently, Professor Kiyono et al. from Tokyo University in Japan have studied it intensively. It is generally known that in case of vaccination via mucosal route, the mucosal immune response is more effectively induced than those via the intrademal or subcutaneous routes, and that the mucosal immune response is mediated mainly by immunoglobulin-A (Ig A).
Vaccination via the mucosal route has an advantage not only in enhancing a systemic immune response but also in enhancing a mucosal immune response simultaneously. For this reason, concerns are amplified on the studies for the development of preventive vaccines that induce effective immune responses in mucosal tissues. However the administration of protein antigens via the mucosal route has a disadvantage that immunogenicity is decreased compared to the administration via the systemic route. Therefore the most important factor in the development of mucosal vaccine is the development of an effective mucosal adjuvant that can be safely adminstered together with vaccine antigens.
One of the most important factors of a vaccine adjuvant is the possession of an immune control function, such as one that controls the expression of co-stimulating molecules of antigen presenting cells and the cytokine secretion induced by antigen specific T-cell induction. Nowadays substances that are in use or concerned as a vaccine adjuvant are mineral salts such as hydroxy aluminium gel, surfactants, substances originating bacteria, cytokine, hormone, polyanions, polyacryls, living vectors using carriers and viruses, and vehicles such as mineral oil or liposome. Among these, the most actively studied and noticed vaccine adjuvants are the protein originated mucosal vaccine adjuvants such as cholera toxin (CT) from Vibrio cholerae and the heat-labile toxin (LT) from Escherichia coli. It was reported that the administration of these vaccine adjuvants via the mucosal tissue route induces the production of antigen-specific antibodies in serum and mucosal tissue, and facilitates co-stimulatory signaling of T-cell induced by expression of B7-2 on the surface of antigen presenting cells. (Boyaka, P. N., Jackson, R. J., Kiyoni, H., Yuki, Y., McGhee, J. R. Immunol. 170:454-462, 2003; Kweon, M. N., Yamamoto, M., Watanabe, F., Tamura, S., Van Ginkel, F. W., Miyauchi, A., Takagi, H., Takeda, Y., Hamabata, T., Fujihashi, K., McGhee, J. R., Kiyono, H. J. Infect.Dis. 186:1261-1269, 2002). However these adjuvants are exotoxins with high enterotoxicity, thus being inadequate to be used directly for human beings. Nowadays worldwide research is being performed with the purpose of making these less toxic but with higher adjuvancity.